Scott Webb: This is HeartSpeak, the podcast from Baylor Scott & White Heart and Vascular Hospital, Dallas and Fort Worth. I'm Scott Webb. And joining me today is Dr. Grant Heberton. He's a cardiologist specializing in heart rhythm disorders on the medical staff of Baylor Scott & White Heart and Vascular Hospital, Dallas.

Dr. Heberton, welcome. As an electrophysiologist, I know you've treated patients who have been newly diagnosed by referring cardiologists as well as patients who found you or maybe another electrophysiologist very late in their atrial fibrillation disease process. It can be understood that patients referred at various stages will have a wide range of outcomes. Recent findings presented at the 2022 American Heart Association Scientific sessions have indicated the critical need for primary care physicians who may be managing patients with AFib or cardiologists who are managing patients with AFib to consider the benefit of early referral to a specialist. So, I want to ask you, what have the findings told us and what should our physician audience know?

Dr. Grant Heberton: So, there have been a number of new studies that have come out recently looking at the benefit of ablation of atrial fibrillation earlier on in the disease process. So, there have been several. In the past couple years, there have been two in particular from the Early AF Investigational Group as well as one called EAST-AFNET. So basically, what these studies have looked at are patients with paroxysmal symptomatic atrial fibrillation and looking at the benefits of early ablation as compared to early use of anti-arrhythmic drugs in the treatment of these patients' disease process.

So most recently, this was a study that enrolled 303 patients, two arms. They essentially put half of them to get anti-arrhythmic drugs at the physician's preference. The other half underwent cryoballoon ablation, and they were followed for a period of three years. So in the initial study that was published in 2021, what they saw was that the ablation group indeed had improvement in both symptomatic outcomes as well as lower rates of AFib, both by patient-reported metrics, but also measured objectively using implantable loop recorders.

On the subsequent followup study that was recently published here in 2022, they were actually looking at a secondary outcome, which was the percentage of patients that were progressing to persistent atrial fibrillation. And so, what they found is that in each group that had approximately 150 patients, 1.9% of patients in the ablation group versus 7.4% of patients in the anti-arrhythmic drug group progressed to persistent atrial fibrillation. And so in addition to the symptomatic benefit that patients derive from this, this gives us some suggestion that early treatment of the disease process may actually prevent the progression of atrial fibrillation and other secondary outcomes that are associated with more severe disease or persistent AFib itself.

Scott Webb: Yeah. So, it does seem like early intervention would be key. And doing some research for our podcast today, I was looking at that AFFIRM trial that was rate versus rhythm control. And it makes me wonder is that something we should still be using to guide decisions?

Dr. Grant Heberton: Yeah. So, the AFFIRM trial was one of the landmark studies looking at the treatment of atrial fibrillation, and it's now almost 20 years old. So if we go back and look at the history of how we've treated atrial fibrillation, catheter ablation is relatively new in the scheme of things. It was first done in the early 1990s. And when they first rolled it out, like with many new technologies, the system was somewhat primitive. Procedure times were extremely long, and it wasn't widely adopted. And as a result of that, most patients for whom rhythm control was desired were treated with anti-arrhythmic drugs.

And so when AFFIRM began enrolling in the late 1990s, they were looking at patients and essentially what they did is they said one group, we're going to treat with rate control and anti-coagulation and the other group we're going to treat with rhythm control primarily with anti-arrhythmic drugs. So, it's really not an ablation trial, it's an anti-arrhythmic drug versus rate control trial. And so when they did the final analysis, when they looked at their primary outcome, which was things like death, stroke, major adverse cardiac events, there was no difference between the two groups. And so, the big headline from this study was there's no benefit to rhythm control over rate control for these patients.

But there are a few things to bear in mind for this study. So, one is the actual use of anti-arrhythmic drugs in the AFFIRM study was associated with a 49% absolute increase in mortality in patients, which was primarily due to non-cardiovascular causes. Conversely, the maintenance of sinus rhythm, in other words, the patients for whom they were able to successfully get them in sinus, had a significantly decreased mortality with a hazard ratio of about 0.53.

There are a couple other things to remember from this trial. And one of the big ones is that in AFFIRM, for patients for whom they were able to get back into rhythm, the study protocol actually dictated that after four weeks in rhythm, they would pull them off of their blood thinner. And in the subsequent analysis, it looks like most of the excess mortality in the rhythm control group was driven by increased rates of stroke. And so, that's the reason that after AFFIRM and up to the present day, we recommend continuation of risk-appropriate anticoagulation for patients regardless of whether we consider them to be successfully rhythm controlled. But if we take a step back from all of this and look at the overall implications of the study, it does suggest that getting patients in rhythm may be beneficial if there was some way to avoid the adverse effects of the anti-arrhythmic drugs. And so, that sort of opened this new field of inquiry into looking at ablation versus antirrhythmic drugs, which is a potentially more effective and also less harmful strategy for maintaining appropriate rhythm control.

Scott Webb: Yeah, I like that. More effective and less harmful, that's sort of, you know, music to my ears. So then, let's talk about the benefits since the AFFIRM trial and what we know now about ablating early on in the disease process.

Dr. Grant Heberton: Like we talked about, subsequent to AFFIRM, there were kind of a few years for which there was sort of this mantra that rate control is just as good, we don't have to do anything else. But what we continue to see, and I think that many clinicians observe this in their clinical practice is that AFib does cause real harm to patients. So, there are the obvious things like symptoms. Patients can feel palpitations, short of breath, decreased exercise tolerance. But then, there are other secondary outcomes that may not manifest upfront, but tend to kind of creep up with time. So, there are obvious things like increased risk of stroke, but there are also associations with increased rates of heart failure, MI and ultimately death.

So as a result of this, we started doing additional studies and there are a few different studies that have been designed a couple different ways. So, there was this one called EAST-AFNET that came out a few years ago that basically looked at early rhythm control versus rate control. In some ways, kind of similar in the idea to AFFIRM, but they did it earlier on. So, there was this idea that maybe if we treat patients earlier before they progressed to persistent or a harder to treat form of AFib, that those patients would be more responsive. And then, there have also been other studies that have been looking at, for those patients for whom we're doing rhythm control strategies, which is more efficacious, is it antirrhythmic drugs or is it catheter ablation? And so, that was the ultimate idea of the Early AF trial, which has now kind of been published in two iterations. The initial trial that basically just looked at overall incidence of AFib, and then the subsequent followup that's been published here this year that looks at progression to persistent AFib. And so, what all of these studies in summation have shown us is that treatment of the rhythm is clearly associated with a decrease in symptoms relative not just to rate control, but even to anti-arrhythmic drug therapy.

And then, there have been other studies that have shown that catheter ablation is superior to rate control for preventing other heart outcomes, so that would be things like heart failure. There was a study that came out in 2018 called CASTLE-AF where they looked at these patients and they showed that patients with heart failure that got ablation actually had lower rates of heart failure-associated hospitalization, lower rates of death, and actually improved ejection fraction on echocardiogram after they underwent ablation for their atrial fibrillation. And so, I think that what we're seeing through all these new studies is that ablating a patient and ablating a patient earlier on before they've progressed to persistent or long-standing persistent when they've had remodeling of the atria can prevent disease progression, improve symptoms, and actually improve heart outcomes like heart failure, death, and other associated endpoints.

Scott Webb: Yeah. Again, music to my ears. And even though this podcast, doctor, is for other physicians, you're explaining this in a way that even I'm understanding you, I'm really following you. So, great to understand this. And it does seem, for me anyway, the biggest takeaway perhaps is that early referral, early intervention, early ablation, all good things. I want to give you a chance though here as we wrap up, what are your takeaways and final thoughts as we move forward? I know you and I were talking before we got going about how things change so quickly. And there's, you know, so many studies and just try to digest all of that information and put it into practice. But what are your takeaways?

Dr. Grant Heberton: Yeah. So, I think that probably the biggest takeaway is that referring a patient early before the disease progresses is a paramount importance in treating them. And so, you know, the analogy I give people is, if somebody had a STEMI and you did their PCI seven days later, it wouldn't really avail them anything to do that, right? You have to do it in a timely manner in order to get the maximum therapeutic. And so, I think that, you know, AFib is a disease process that's progressive. There's this old mantra that AFib begets AFib, that the longer period of time that someone is in AFib, they get more scarring. It becomes harder to control, it becomes more symptomatic. And so, those patients that are seen early and potentially treated early have much better outcomes. And so, there's been this advent of this concept of time to ablation or at least time to treatment in these patients who are eligible as a potential therapeutic option to improve their outcomes.

Now, that's not to say that ablation is the right thing for every patient. It depends on the individual, how symptomatic they are, sort of what their overall goals are. But I think that for a significant number and probably for far more patients than we're currently doing, I think getting them into rhythm is something that can help them feel better and potentially help them live longer and more productive lives.

Scott Webb: Yeah, feel better, live longer. It's all good stuff. So again, doctor, thanks for explaining this in a way that I could understand, but I'm sure it was very beneficial to other providers, other physicians. So, thanks so much for your time. You stay well.

Dr. Grant Heberton: Thank you so much. I appreciate it.

Scott Webb: And for more information, call the Heart Rhythm Center in Dallas at 214-820-5306 or the Heart Rhythm Center in Fort Worth at 814-825-1374.

Scott Webb (Host): Thanks for listening to HeartSpeak, the podcast for Baylor Scott & White Heart and Vascular Hospital in Dallas and Fort Worth. If you found this podcast helpful, please share it on your social channels and be sure to check out the entire podcast library for additional topics of interest. I'm Scott Webb. Thanks for listening.

Host: Baylor Scott & White Heart and Vascular Hospital, Dallas and Fort Worth, joint ownership with physicians.